| CTRI Number |
CTRI/2025/10/096554 [Registered on: 29/10/2025] Trial Registered Prospectively |
| Last Modified On: |
28/10/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
Use of Combination therapy versus Azithromycin or
Doxycycline monotherapy in Children suffering from scrub typhus |
|
Scientific Title of Study
|
Efficacy in Scrub typhus of Combination therapy in Children versus Azithromycin or
Doxycycline monotherapy: a double-blind Randomized control trial (ESCHAR Trial) |
| Trial Acronym |
ESCHAR Trial |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Vidushi Mahajan |
| Designation |
Associate Professor |
| Affiliation |
Government Medical College and Hospital Chandigarh |
| Address |
D Block, level 4, Room No. 411, Government Medical College and Hospital, Sector 32,Chandigarh
Chandigarh
CHANDIGARH
160030
India |
| Phone |
9646121531 |
| Fax |
|
| Email |
vidushimahajan2003@yahoo.co.in |
|
Details of Contact Person
Scientific Query
|
| Name |
Vidushi Mahajan |
| Designation |
Associate Professor |
| Affiliation |
Government Medical College and Hospital Chandigarh |
| Address |
D Block, level 4, Room No. 411, Government Medical College and Hospital, Sector 32,Chandigarh
Chandigarh
CHANDIGARH
160030
India |
| Phone |
9646121531 |
| Fax |
|
| Email |
vidushimahajan2003@yahoo.co.in |
|
Details of Contact Person
Public Query
|
| Name |
Vidushi Mahajan |
| Designation |
Associate Professor |
| Affiliation |
Government Medical College and Hospital Chandigarh |
| Address |
D Block, level 4, Room No. 411, Government Medical College and Hospital, Sector 32,Chandigarh
Chandigarh
CHANDIGARH
160030
India |
| Phone |
9646121531 |
| Fax |
|
| Email |
vidushimahajan2003@yahoo.co.in |
|
|
Source of Monetary or Material Support
|
| Indian Council of Medical Research, New Delhi, India |
|
|
Primary Sponsor
|
| Name |
Indian Council of Medical Research |
| Address |
Ansari Nagar,New Delhi, India |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Lokesh Tiwari |
All India Institute of Medical Sciences |
Rishikesh
Dehradun
UTTARANCHAL |
9631638095
lokeshdoc@yahoo.com |
| Dr Rashmi Ranjan Das |
All India Institute of Medical Sciences |
Bhubaneshwar
Khordha
ORISSA |
9937410288
rrdas05@gmail.com |
| Dr Milap Sharma |
Dr. Rajendra Prasad Government Medical College and Hospital |
Tanda
Kangra
HIMACHAL PRADESH |
9418079463
dr.milapsharma66@gmail.com |
| Dr Vidushi Mahajan |
Government Medical College and Hospital Chandigarh |
Sector 32, Chandigarh
Chandigarh
CHANDIGARH |
9646121531
vidushimahajan2003@yahoo.co.in |
| Dr Parveen Bhardwaj |
Indira Gandhi Medical College and Hospital |
Shimla
Shimla
HIMACHAL PRADESH |
7018954431
parveenbhardwaj@hotmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Dr. Rajendra Prasad Government Medical College (Dr. RPGMC) Kangra at Tanda, Himachal Pradesh, India Institutional Ethics Committee (IEC) |
Approved |
| INSTITUTE ETHICS COMMITTEE, ALL INDIA INSTITUTE OF MEDICAL SCIENCES BHUBANESHWAR |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE(GMCH, Chandigarh) |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE, ALL INDIA INSTITUTE OF MEDICAL SCIENCES RISHIKESH |
Approved |
| Institutional Ethics Committee, IGMC Shimla |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: A753||Typhus fever due to Rickettsia tsutsugamushi, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Group 1: Doxycycline plus placebo for 7 days.
|
Group 1: Doxycycline 4.5 mg/ kg/d in two divided doses for children less than 40 kg and 100 mg twice daily for children above 40 kg plus placebo, for 3 days after subsidence of fever or a total 7 days.
|
| Comparator Agent |
Group 2: Azithromycin plus placebo for 7 days |
Group 2: Azithromycin 10 mg/kg/day in two divided doses plus placebo for 7 days. |
| Intervention |
Group 3: Combination therapy |
Group 3: Combination therapy ( Azithromycin and doxycycline at above dosages) |
|
|
Inclusion Criteria
|
| Age From |
0.08 Year(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
Participants eligible for inclusion in the trial if they meet all the following criteria:
Children aged 1 month-18 years
Suffering from scrub typhus (acute febrile illness of atleast 5 days) with a positive result on Scrub Typhus Rapid diagnostic test or presented with an eschar.
Atleast one organ -system involvement as per the Pediatric sequential organ failure assessment (pSOFA) scoring
Fever of less than 5 days will be considered in case of co-presence of eschar or positive scrub RDT or IgM serology with cutoff optical density greater than or equal to 0.5 or a positive RT-PCR report.
|
|
| ExclusionCriteria |
| Details |
Participants will be excluded if they meet any of the following criteria:
• Prior treatment with tetracyclines, macrolides, rifampicin or chloramphenicol for more than 24
hours within 48 hours before recruitment.
• Lethal congenital anomaly or known immundeficiency.
• History of hypersensitivity to macrolides or tetracylines
• Denied consent |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
• The primary outcome will be a composite of all-cause mortality within 14 days, persistent
complications on day 7, and persistent fever ( more than 37.5°C) on day 5.
|
14 days, day 7, day 5.
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Secondary outcome: will include 14-day all-cause mortality, fever defervescence at day 5, Time to fever resolution, persistent complications at day 7, hospitalization stay, and adverse events. |
Day 5, Day 7 and Day 14 |
|
|
Target Sample Size
|
Total Sample Size="649"
Sample Size from India="649"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
01/01/2026 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
(i) Scrub typhus, caused by rickettsia Orientia tsutsugamushi, can lead to multi-organ dysfunction and high mortality. Doxycycline and azithromycin are the standard drug treatment available. Recent findings suggest that combination therapy may offer superior outcomes in adults. Keeping in mind antimicrobial stewardship, high-quality, clinical trials evaluating the efficacy and safety of this combination in children below 18 years are needed. (ii) Novelty: To assess the comparative effectiveness of monotherapy versus combination therapy to determine whether combination therapy should become the standard-of-care for severe scrub typhus in children 1 month to 18 years. (iii) Objectives: To compare combination therapy versus monotherapy for a composite outcome of all- cause mortality within 14 days, persistent complications on day 7, and persistent fever ( more than 37.5°C) on day 5, amongst children 1 month to 18 years years presenting with severe scrub typhus..
To compare all-cause 14-day mortality, fever resolution by day 5, organ dysfunction and adverse effects profile between combination therapy vs. monotherapy in the above defined population. (iv) Methods: Study Design: A multi-center, double blind parallel arm, randomized control trial. Study Population: Patients aged 1-month to18 years with severe scrub typhus and at least one organ involvement. Intervention: Group 1: Doxycycline 4.5 mg/ kg/d in two divided doses for children less than 40 kg and 100 mg twice daily for children above 40 kg plus placebo, for 3 days after subsidence of fever or a total 7 days. Group 2: Azithromycin 10 mg/kg/day in two divided doses plus placebo for 7 days. Group 3: Combination therapy (both drugs at the above dosages). Outcome Measures: Primary outcome: will be a composite of all-cause mortality within 14 days, persistent complications on day 7, and persistent fever ( more than 37.5°C ) on day 5. Secondary outcome: 14-day all-cause mortality, fever defervescence at day 5, Time to fever resolution, persistent complications at day 7, hospitalization stay, and adverse events. (v) Expected Outcome: The study will provide robust evidence on whether combination therapy vs. monotherapy reduces severe scrub typhus complications and mortality. |